Download Access to inhaled corticosteroids is key to improving quality of care

Ó 2007 The Authors
Journal compilation Ó 2007 Blackwell Munksgaard
Allergy 2007: 62: 230–236
DOI: 10.1111/j.1398-9995.2007.01326.x
Review article
Access to inhaled corticosteroids is key to improving quality of
care for asthma in developing countries
Asthma is a worldwide public health problem affecting about 300 million people. The majority of persons living with asthma are in the developing world
where there is limited access to essential drugs. The financial burden for persons
living with asthma and their families, as well as for healthcare systems and
governments, is very high. Inadequate treatment and the high cost of medications leads to disability, absenteeism and poverty. Despite the existence of
effective asthma medications and international guidelines, and progress made in
the implementation of such guidelines over the last decade, the high cost of
essential asthma medications remains a major obstacle for patient access to
treatment in developing countries.The International Union Against Tuberculosis
and Lung Disease has evaluated this problem and created an Asthma Drug
Facility (ADF) so that countries can purchase affordable, good quality essential
drugs for asthma. The ADF uses pooled procurement along with other purchasing and supply strategies to obtain the lowest possible prices. Accompanied
by the implementation of standardized asthma management, the increased affordability of drugs provided by the ADF should bring rapid and significant
health and cost benefits for patients, their communities and governments.
Asthma is a worldwide public health problem affecting
about 300 million people. The majority of those living
with asthma are in the developing world where there is
limited access to essential drugs (1). The financial burden
is very high for persons living with asthma, for their
families, as well as for healthcare systems and governments (2–6). Costs increase dramatically when the quality
of case management is poor (7). Inadequate treatment
and high costs of medications lead to disability, absenteeism and poverty (8, 9). An effective case management
strategy for the diagnosis, treatment and monitoring of
asthma has been developed. It has been successfully
evaluated in pilot studies conducted by the International
Union Against Tuberculosis and Lung Disease (The
Union) in health institutions in several developing countries (10, 11). Despite the existence of effective medications and international guidelines, and progress made in
the implementation of such guidelines over the last
decade, the continued high cost of essential asthma
medications constitutes a major obstacle for patient
access to treatment in the majority of developing countries.
A key conclusion of the first World Asthma Meeting, a
joint meeting in 1998 of experts from six scientific
societies, was: ÔThere is a huge need for an international
230
N. Ait-Khaled, D. A. Enarson,
K. Bissell, N. E. Billo
International Union against Tuberculosis and Lung
Disease (The Union), Paris, France
Key words: asthma; developing countries; essential
medicines; inhaled corticosteroids; quality of care.
Prof. Nadia Ait-Khaled
International Union against Tuberculosis and Lung
Disease (The Union)
68, Boulevard Saint-Michel
75006 Paris
France
Accepted for publication 8 January 2007
action for making effective asthma therapy available in all
countries all over the worldÕ (12).
The increasing problem of asthma in developing countries
Phase I of the International Study of Asthma and
Allergies in Childhood (ISAAC) calculated the cumulative prevalence of asthma in children aged 13–14 years in
155 centres in 58 countries. The highest prevalence rates
were found in Oceania (25.9%) and North America
(16.5%), slightly lower rates in Latin America (13.4%),
western Europe (13%), the eastern Mediterranean
(10.7%), Africa (10.4%) and Asia Pacific (9.4%), and
the lowest in South-East Asia (4.5%) and eastern Europe
(4.4%). The prevalence of asthma is not only higher in
industrialized countries, but also is already worryingly
high in Latin America, in the eastern Mediterranean and
in Africa (13–15).
Conducted 5–6 years later using the same methodology, Phase III of the ISAAC study confirmed the high
prevalence of asthma symptoms in some of the developing country centres. An increasing trend in asthma
symptom prevalence was observed in the majority of
centres in developing countries, particularly in the urban
Improving quality of care for asthma
centres, whereas a stabilization or decrease was observed
in the majority of centres in industrialized countries (16).
With the projected increase in the proportion of the
world’s population that is urban from 45% to 59% in
2025, it is estimated that there may be an additional
100 million persons with asthma by 2025 (1).
The moderate or high prevalence of asthma in some
developing countries is already being reflected by a
significant demand for health services. Thus, surveys
conducted in several countries prior to the implementation of the ÔPractical Approach to Lung HealthÕ (PAL), a
WHO initiative for the standardized management of
respiratory diseases (17), demonstrated that asthma is the
first cause of consultation for chronic respiratory disease
in primary healthcare settings and at the first level of
referral in nine developing countries (18).
Mortality rates (asthma death rate per 100 000
inhabitants) and fatality rate (asthma death rate per
100 000 asthmatics) are available for relatively few
countries. These rates vary among countries and are
not directly related to asthma prevalence. From 1985 to
1987, the estimated fatality rates in industrialized
countries varied from 2 in the USA and Hong-Kong,
to 7 in New Zealand, and more than 9 in Germany
(19). These deaths occurred mainly among the young
and in 50–60% of cases, at the patient’s home, after
asthma attacks the severity of which were underestimated and under-treated, and in individuals who
had not been given long-term treatment or had been
given an inappropriate long-term treatment. For these
reasons, in some countries this rate was much higher in
disadvantaged population groups: it was three times
higher among blacks than among whites in the USA,
and five times higher in the Maori population than the
European population in New Zealand (20).
In most industrialized countries, the rising trend in
mortality previously observed has stopped or has been
reversed since 1990 (21). This decrease in mortality,
despite a rise in prevalence, is probably linked to better
use of inhaled corticosteroids among those who have
access to such medication. This decrease was confirmed
by estimations of the asthma fatality rate among
patients of 5–34 years of age for the years 1996 and
1997 in several countries (1). Case fatality was low
(<5) in most of industrialized countries, with variations
from 1.6 in Finland and 4.6 in New Zealand, to 9.3 in
Denmark. The highest fatality rates (>10) were found
in several developing countries, such as Colombia (10),
Mexico (14.5), South Africa (18.7) and China (36.7).
Asthma morbidity has increased worldwide over the
last 20 years (1), and is reflected in increased hospitalization. The dissemination of consensus recommendations
seems to have stemmed this trend in some industrialized
countries. But even in these countries, unplanned use of
health services is higher among the poor. It has been
linked to deficiencies in patient management, lack of
access to care, absence or under-utilization of inhaled
corticosteroids and lack of patient health education
(22–24).
The cost of asthma increases with ineffective management
practices
The cost of asthma (2) includes direct costs (e.g. the cost
of medications, consultations, hospitalizations), indirect
costs linked to loss of productivity (e.g. days absent from
work or school, job losses, premature death), and
intangible costs, which are often considerable but difficult
to calculate (e.g. effects on family and social life, sporting
activities, and professional or emotional repercussions).
There is a lack of data regarding the overall cost of
asthma morbidity and mortality in developing countries. The cost of the disease can only be estimated
using data from industrialized countries. In industrialized countries, the rising trend in asthma morbidity
over the last 20 years has been reflected in an increase
in hospitalizations and healthcare costs. In 1990, it was
estimated that annual asthma costs in the USA were
US$ 640 per patient and that they represented 0.5–
1.0% of all USA healthcare expenditure. In 1998, the
annual cost of asthma in the USA was estimated to be
US$ 12.7 billion, more than twice the annual cost from
1990 (25). In 1999, the prevalence of asthma in
Germany’s statutory health insurance system was
6.3% and the total cost of asthma amounted to
€2.74 billion (26). Annual asthma costs vary among
countries (27), from US$ 1315 in Sweden in 1975 to
US$ 326 per patient in Australia in 1991. The cost of
asthma per patient has consistently been found to be
higher for the highest grade of severity and to rise
dramatically with an increase in emergency room visits
and hospitalizations (28–31).
The total cost of asthma is estimated to be at least US$
20 billion annually in developing countries alone.
Although the disease is frequent, many cases do not
receive adequate diagnosis and treatment, which exacerbates the condition and means additional costs. For more
accurate estimations of the disease burden in developing
countries; however, much more research into asthma
costs for the individual and society as a whole is needed.
The number of disability adjusted life years (DALYs)
lost is a useful way to compare the relative importance of
chronic respiratory diseases. Using this approach, it was
estimated that respiratory diseases caused 15% of the
global burden of disease in 1999, with chronic obstructive
pulmonary disease (COPD) contributing 2.7% of the
burden, tuberculosis 2.3% and asthma 0.9%. However,
there were significant differences among regions of the
world (32, 33). The number of DALYs lost worldwide
due to asthma has been estimated at about 15 million/
year, which accounts for about 1% of all DALYs lost,
Ôsimilar to that for diabetes, cirrhosis of the liver or
schizophreniaÕ (1).
231
Ait-Khaled et al.
Cost-effective standardized case management is possible
International guidelines have been widely disseminated
throughout the world (34). Several national consensus
documents, recommendations and guides have also been
published. The cost-effectiveness of inhaled drugs, in
particular inhaled corticosteroids, has been demonstrated
in many countries and is well known by health workers.
Costs associated with asthma can be reduced by
appropriate case management and the introduction of
high-dose inhaled corticosteroids for patients with persistent asthma. The number of hospital days for such
patients can be reduced by up to 80%, which entails a
significant reduction in costs for the health services (35).
The Union Asthma guide, published in 1996 (36) and
revised in 2005 (37), proposes a technical package for
asthma management, based on the management model
developed for tuberculosis control, known as the DOTS
strategy (internationally-recommended tuberculosis control strategy), which is implemented within the clinical
general health services. This standardized asthma management approach recommends the use of two drugs,
both of which are included in the World Health Organization’s Model List of Essential Medicines: inhaled
beclomethasone 250 lg per puff and inhaled salbutamol
100 lg per puff (Fig. 1). As for tuberculosis information
systems, the use of a register is recommended for asthma
management. Each new patient with persistent asthma is
registered, and key information about his or her initial
status and status during follow up is entered into the
register. Case notification and patient outcome can
therefore be routinely analysed using the register.
Pilot studies of The Union asthma management
approach were conducted in Algeria, Morocco, Vietnam
and Syria from 1998 to 1999. The 1-year follow up of 167
patients (11) found that the severity of asthma had
decreased dramatically for the majority of patients
(Fig. 2), and the number of emergency visits and hospitalizations had decreased by more than 70% (Fig. 3).
Thus, the implementation of standardized management
of asthma using effective essential medicines can significantly reduce costs for patients, their families, societies
and governments. In addition, by increasing the quality
of services for respiratory patients, it will enhance the
credibility of public health services in general, and attract
more patients with respiratory symptoms, in particular,
those with chronic cough.
Low affordability of essential asthma drugs is a key barrier
for standardized case management
Despite the demonstrated cost-effectiveness of standardized asthma management using high-dose inhaled beclomethasone, this medicine has not been available in a large
number of developing countries in recent years. In other
developing countries, it is available but not affordable for
the majority of patients.
In a 1998 Union study, inhaled beclomethasone was
found to be consistently available in only four of the eight
countries surveyed. The cost of inhaled beclomethasone
varied more than fivefold and for inhaled salbutamol
more than threefold. In general, the highest prices were
observed in the poorest countries. In all but two
Figure 1. Four-step approach to asthma with chlorofluorocarbons (CFC)-free inhalers; beclomethasone 250 lg and salbutamol
100 lg.
232
Improving quality of care for asthma
Change in asthma severity before and after standardised
management for the 167 patients still on followup after one year
Proportion of patients
60
50
40
Before
30
After
20
10
0
intermittent
mild
moderate
persistent
persistent
Asthma severity
severe
persistent
Figure 2. Asthma treatment efficacy with essential asthma drugs. Implementation of The Union Asthma Guide (Algeria, Morocco,
Syria and Vietnam).
Nb events
160
ER visits
Hospitalisation
140
Cost of drugs for one year in 1998
for 1 case of moderate persistent asthma
compared with the monthly salary of a nurse
Drug cost
120
Algeria
100
Vietnam
Syria
80
Guinea
60
Mali
40
Ivory Coast
Burkina Faso
20
0
Nurse's salary
Turkey
0
Before
50
100
150
200
250
300
350
After
Figure 4. Low affordability of asthma drugs.
Figure 3. Treatment cost-effectiveness with asthma essential
drugs. Implementation of The Union guide (Algeria, Morocco,
Syria and Vietnam).
countries, the cost of 1 year of treatment for a case of
moderate persistent asthma exceeded the monthly salary
of a nurse. In addition, patients did not have health
insurance in six of these countries (38). It is clear that
under these conditions the patients could not be treated
with inhaled steroids (Fig. 4).
The next survey, conducted in eastern Europe, showed
that inhaled beclomethasone was generally unavailable in
Azerbaijan, Georgia and the Russian Federation. In six
other countries, however, drugs were available and
affordable. The situation was particularly positive in
Poland, where 1 year of treatment for one case of
moderate persistent asthma with drugs produced in
Poland cost only US$ 20 (8).
In 2002 and 2003, The Union surveyed drug prices in
several other countries (8). Results confirmed large
variations in drug prices. For example, the price of one
inhaler with 200 doses of inhaled beclomethasone
250 lg was US$ 62 in Kuwait, US$ 25 in Sudan,
US$ 32 in France and $ 4 in Algeria. The same price
variation was observed for salbutamol within countries
(US$ 2.20 to US$ 8.75). The average price for 1 year of
treatment for one case of moderate persistent asthma
varied from US$ 688 in Kuwait to US$ 36 for country
buying generics (with an order of at least 10 000
inhalers of each drug).
Several other studies have highlighted the problem of
low affordability of asthma drugs. Preliminary results
from the Global Asthma Survey on Practice (GASP), an
audit of emergency room treatment of asthma in several
countries in 2003, showed that the main factor associated
with emergency visits is low affordability for patients of
the drugs used for long-term treatment of asthma (39).
Other studies have found that emergency admissions are
associated with patientsÕ lack of or poor health insurance
233
Ait-Khaled et al.
coverage for asthma medications (40, 41) and with
socioeconomic deprivation (23, 40).
It is evident, then, that affordable essential asthma
drugs are still not reaching patients in developing
countries and that the low affordability of essential
asthma drugs remains the main barrier for the adequate
management of asthma.
Improving access to affordable medications
In order to improve the access and affordability of
essential asthma medicines in low- and middle-income
countries, The Union has created the Asthma Drug
Facility (ADF; 42, 43). The ADF has drawn lessons from
The Union’s experiences in medicine procurement in the
1990s (44) and the Stop TB Partnership’s Global Drug
Facility (GDF), created in 2001 (45). Countries or organizations within countries can purchase affordable, good
quality essential medicines for asthma through the ADF.
The ADF uses pooled procurement and other purchasing
and supply strategies to obtain the lowest possible prices.
Delivery is organized by the ADF’s procurement agent. As
the implementation of quality healthcare services is a key
concern of the ADF and The Union, technical resources
and monitoring will also be provided and clients will be
required to submit reports on patient management.
The ADF supplies the following inhaled drugs in CFCfree and CFC-containing formulations: salbutamol
100 lg, terbutaline 250 lg, beclomethasone 250 lg, budesonide 200 lg and fluticasone 125 lg. These are available as pressured meter-dose inhalers propelled either by
chlorofluorocarbons (CFCs) or hydrofluoroalkanes
(HFAs).
In accordance with the Montreal Protocol on Substances that Deplete the Ozone Layer, and its subsequent
amendments, many industrialized countries have now
stopped producing and importing CFC-containing products. For asthma treatment, the Protocol required that
CFC-containing inhalers be phased out in the majority of
countries by 2005 (46, 47). In parallel, HFA-propelled
asthma inhalers have been produced. Studies of the
bioavailability, pharmacokinetics, efficacy, improvement
in quality of life and toxicity of HFA inhalers have been
conducted mainly on salbutamol and beclomethasone.
HFA formulations of salbutamol have been judged
comparable with those containing CFCs (48–51). How-
ever, HFA beclomethasone has proved effective and less
toxic at lower doses: the dose equivalence between HFAbeclomethasone and CFC-beclomethasone is approximately 2 to 1 (52–59). Thus, the number of puffs per day
for HFA-beclomethasone (Fig. 1) becomes half of the
number recommended for CFC-beclomethasone in The
Union guide (37).
As the prices obtained by the ADF for these two
beclomethasone inhalers are very similar, the use of HFA
inhalers will significantly decrease the price of treatment.
Two studies comparing the cost and effectiveness of these
two formulations of beclomethasone (CFC and HFA at
half the dose) have shown that HFA beclomethasone is
more cost-effective (60, 61).
Conclusion
World Health Organization has recently highlighted the
importance of chronic diseases, notably with its publication ÔPreventing chronic diseases: a vital investmentÕ (62).
However, there are today many competing public health
priorities (AIDS, tuberculosis, malaria, avian flu, etc.). It
is difficult to convince donors and governments that
chronic respiratory diseases, such as asthma, represent a
huge burden to healthcare systems all over the world.
This challenge was emphasized at the launch of the
Global Alliance against Chronic Respiratory Diseases
(GARD) in Beijing on the 28 of March 2006 (63).
The availability of affordable CFC-free asthma medicines through the ADF (leading to annual treatment costs
for one case of persistent asthma of <30 USD) and the
introduction of standardized case management will allow
governments to save millions in costs for medicines and
unnecessary emergency room visits and hospitalizations.
Clinical services will be able to provide a more complete
response for patients presenting with respiratory problems. This should improve the credibility of the public
health sector and other services that can provide quality
asthma care, thus strengthening health systems in general.
Most importantly, affordable asthma drugs will contribute to poverty alleviation by reducing the burden on
governments, hospitals, persons and families affected by
asthma. Improved access and standardized management
should be advocated by all those interested in public
health with as much force, enthusiasm and perseverance
as is dedicated to AIDS, tuberculosis and malaria (43).
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